Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction

Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction

Multi-scale polarisation phenomena

Multi-scale methods that separate different time or spatial scales are among the most powerful techniques in physics, especially in applications that study nonlinear systems with noise. When the time scales (noise and perturbation) are of the same order, the scales separation becomes impossible. Thus, the multi-scale approach has to be modified to characterise a variety of noise-induced phenomena. Here, based on stochastic modelling and analytical study, we demonstrate in terms of the fluctuation-induced phenomena and Hurst R/S analysis metrics that the matching scales of random birefringence and pump–signal states of polarisation interaction in a fibre Raman amplifier results in a new random birefringence-mediated phenomenon, which is similar to stochastic anti-resonance. The observed phenomenon, apart from the fundamental interest, provides a base for advancing multi-scale methods with application to different coupled nonlinear systems ranging from lasers (multimode, mode-locked, random, etc.) to nanostructures (light-mediated conformation of molecules and chemical reactions, Brownian motors, etc.)

Age and the Neural Network of Personal Familiarity

BACKGROUND: Accessing information that defines personally familiar context in real-world situations is essential for the social interactions and the independent functioning of an individual. Personal familiarity is associated with the availability of semantic and episodic information as well as the emotional meaningfulness surrounding a stimulus. These features are known to be associated with neural activity in distinct brain regions across different stimulus conditions (e.g., when perceiving faces, voices, places, objects), which may reflect a shared neural basis. Although perceiving context-rich personal familiarity may appear unchanged in aging on the behavioral level, it has not yet been studied whether this can be supported by neuroimaging data. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging to investigate the neural network associated with personal familiarity during the perception of personally familiar faces and places. Twelve young and twelve elderly cognitively healthy subjects participated in the study. Both age groups showed a similar activation pattern underlying personal familiarity, predominantly in anterior cingulate and posterior cingulate cortices, irrespective of the stimulus type. The young subjects, but not the elderly subjects demonstrated an additional anterior cingulate deactivation when perceiving unfamiliar stimuli. CONCLUSIONS/SIGNIFICANCE: Although we found evidence for an age-dependent reduction in frontal cortical deactivation, our data show that there is a stimulus-independent neural network associated with personal familiarity of faces and places, which is less susceptible to aging-related changes

Basin-wide variations in Amazon forest nitrogen-cycling characteristics as inferred from plant and soil ¹⁵N:¹⁴N measurements

Background: Patterns in tropical forest nitrogen cycling are poorly understood. In particular, the extent to which leguminous trees in these forests fix nitrogen is unclear. Aims: We aimed to determine factors that explain variation in foliar δ¹⁵N (δ¹⁵NF) for Amazon forest trees, and to evaluate the extent to which putatively N₂-fixing Fabaceae acquire nitrogen from the atmosphere. Methods: Upper-canopy δ¹⁵NF values were determined for 1255 trees sampled across 65 Amazon forest plots. Along with plot inventory data, differences in δ¹⁵NF between nodule-forming Fabaceae and other trees were used to estimate the extent of N² fixation. Results: δ¹⁵NF ranged from −12.1‰ to +9.3‰. Most of this variation was attributable to site-specific conditions, with extractable soil phosphorus and dry-season precipitation having strong influences, suggesting a restricted availability of nitrogen on both young and old soils and/or at low precipitation. Fabaceae constituted fewer than 10% of the sampled trees, and only 36% were expressed fixers. We estimated an average Amazon forest symbiotic fixation rate of 3 kg N ha¯¹ year‾¹. Conclusion: Plant δ¹⁵N indicate that low levels of nitrogen availability are only likely to influence Amazon forest function on immature or old weathered soils and/or where dry-season precipitation is low. Most Fabaceae species that are capable of nodulating do not fix nitrogen in Amazonia

Pre–B cell receptor–mediated cell cycle arrest in Philadelphia chromosome–positive acute lymphoblastic leukemia requires IKAROS function

B cell lineage acute lymphoblastic leukemia (ALL) arises in virtually all cases from B cell precursors that are arrested at pre–B cell receptor–dependent stages. The Philadelphia chromosome–positive (Ph+) subtype of ALL accounts for 25–30% of cases of adult ALL, has the most unfavorable clinical outcome among all ALL subtypes and is defined by the oncogenic BCR-ABL1 kinase and deletions of the IKAROS gene in >80% of cases. Here, we demonstrate that the pre–B cell receptor functions as a tumor suppressor upstream of IKAROS through induction of cell cycle arrest in Ph+ ALL cells. Pre–B cell receptor–mediated cell cycle arrest in Ph+ ALL cells critically depends on IKAROS function, and is reversed by coexpression of the dominant-negative IKAROS splice variant IK6. IKAROS also promotes tumor suppression through cooperation with downstream molecules of the pre–B cell receptor signaling pathway, even if expression of the pre–B cell receptor itself is compromised. In this case, IKAROS redirects oncogenic BCR-ABL1 tyrosine kinase signaling from SRC kinase-activation to SLP65, which functions as a critical tumor suppressor downstream of the pre–B cell receptor. These findings provide a rationale for the surprisingly high frequency of IKAROS deletions in Ph+ ALL and identify IKAROS-mediated cell cycle exit as the endpoint of an emerging pathway of pre–B cell receptor–mediated tumor suppression

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Study on psychoeducation enhancing results of adherence in patients with schizophrenia (SPERA-S): study protocol for a randomized controlled trial.

BACKGROUND: Poor adherence to pharmacotherapy negatively affects the course and the outcome of schizophreniaspectrum psychoses, enhancing the risk of relapse. Falloon and coworkers developed a Psychoeducation Program aimed at improving communication and problem-solving abilities in patients and their families. This study set out to evaluate changes in adherence to pharmacotherapy in patients diagnosed with schizophrenia-spectrum psychoses, by comparing one group exposed to the Falloon Psychoeducation Program (FPP) with another group exposed to family supportive therapy with generic information on the disorders. METHODS: 340 patients diagnosed with schizophrenia and related disorders according to standardized criteria from 10 participating units distributed throughout the Italian National Health System (NHS), will be enrolled with 1:1 allocation by the method of blocks of randomized permutations. Patients will be reassessed at 6, 12 and 18 months after start of treatment (duration: 6 months).The primary objective is to evaluate changes in adherence to pharmacotherapy after psychoeducation. Adherence will be assessed at three-month intervals by measuring blood levels of the primary prescribed drug using high pressure liquid chromatography, and via the Medication Adherence Questionnaire and a modified version of the Adherence Interview. Secondary objectives are changes in the frequency of relapse and readmission, as the main indicator of the course of the disorder.Enrolled patients will be allocated to the FPP (yes/no) randomly, 1:1, in a procedure controlled by the coordinating unit; codes will be masked until the conclusion of the protocol (or the occurrence of a severe negative event). The raters will be blind to treatment allocation and will be tested for blinding after treatment completion. Intention-to-treat will be applied in considering the primary and secondary outcomes. Multiple imputations will be applied to integrate the missing data. The study started recruitment in February 2013; the total duration of the study is 27 months. DISCUSSION: If the psychoeducation program proves effective in improving adherence to pharmacotherapy and in reducing relapse and readmissions, its application could be proposed as a standard adjunctive psychosocial treatment within the Italian NHS

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection

High recombination rates and hotspots in a Plasmodium falciparum genetic cross

Using the universal P2/P8 primers, we were able to obtain the gene segments of chromo-helicase-DNA binding protein (CHD)-Z and CHD-W from ten species of ardeid birds including Chinese egret (Egretta eulophotes), little egret (E. garzetta), eastern reef egret (E. sacra), great egret (Ardea alba), grey heron (A. cinerea), Chinese pond-heron (Ardeola bacchus), cattle egret (Bubulcus ibis), black-crowned night-heron (Nycticorax nycticorax), cinnamon bittern (Ixobrychus cinnamomeus) and yellow bittern (I. sinensis). Based on conserved regions inside the P2/P8-derived sequences, we designed new PCR primers for sex identification in these ardeid species. Using agarose gel electrophoresis, the PCR products showed two bands for females (140 bp derived from CHD-W and the other 250 bp from CHD-ZW), whereas the males showed only the 250 bp band. The results indicated that our new primers could be used for accurate and convenient sex identification in ardeid species.National Natural Science Foundation of China[30970380, 40876077]; Fujian Natural Science Foundation of China[2008S0007, 2009J01195